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ObesityAugust 2023Summary reviewed May 2026

What the Retatrutide Phase 2 Trial Found — A Triple-Hormone Drug for Weight Loss

This Phase 2 study tested retatrutide, a once-weekly injection that activates three gut hormones at once (GLP-1, GIP, and glucagon), in 338 adults with obesity but without diabetes. At 48 weeks, people on the highest dose lost an average of ~24% of their body weight — bigger than what either semaglutide or tirzepatide trials have shown.

What the trial was testing

The Retatrutide Phase 2 enrolled 338 patients with obesity. The study was sponsored by Eli Lilly and Company and tracked outcomes across the full group of patients who matched the trial's eligibility profile.

It was a mid-stage trial — researchers are testing whether the treatment actually works for the condition. Trials at this stage are designed to produce evidence regulators and physicians can act on — not just observations to follow up later.

What the results showed

~24% average body weight loss on the highest retatrutide dose at 48 weeks.

New England Journal of Medicine · 2023 · NCT04881760

These findings — that average body weight loss on highest-dose weekly retatrutide vs. placebo at 48 weeks — were published in the New England Journal of Medicine and represent the headline result of the study.

Researchers tracked outcomes across 338 patients enrolled in the trial. The result was consistent enough across the group that the team felt confident reporting it.

What this means for patients

For patients with obesity, this result changes the calculus on what to ask their care team about. Whether it changes day-to-day care depends on factors like disease subtype, prior treatments, and where the patient is in their care journey.

What you can do now

Retatrutide is NOT YET FDA-approved — it's in Phase 3 trials (the TRIUMPH program) and not commercially available. Phase 3 results are expected in 2026-2027; commercial availability would follow if results hold up. If you're interested in retatrutide trials, ask your doctor whether you might qualify, or search for active retatrutide trials on Stella or ClinicalTrials.gov.

Eligibility for the treatments mentioned above depends on specific test results and clinical history. Bring this summary, the trial name, and your most recent labs or pathology report to your next visit.

Open obesity trials

RecruitingObservational study

Metabolic Phenotyping for Personalized Obesity Therapy

This study aims to develop a simple, clinically applicable method for metabolic phenotyping to personalize obesity therapy in morbidly obese individuals. The underlying concept is that the way a person's resting metabolic rate (RMR) responds to a 24-hour fast can help distinguish between two metabolic phenotypes. Individuals with a "thrifty" metabolism show a significant drop in RMR during fasting, which may make them less responsive to conventional weight loss interventions. In contrast, those with a "spendthrift" metabolism exhibit little to no drop-or even a slight increase-in RMR, suggesting they may lose weight more readily. The trial is designed as a prospective, single-center, longitudinal cohort study involving 20 morbidly obese patients (BMI \>40 kg/m²) who are already participating in a multimodal obesity therapy program. The study is divided into three phases. In the baseline phase, participants undergo comprehensive screening, which includes physical examinations, blood tests, and body composition assessments. RMR is measured using indirect calorimetry both before and after a 24-hour fasting period, and a device (Lumen™) is used to assess whether the body is primarily burning carbohydrates or fats. After the fasting measurements, participants perform a low-protein meal test by consuming a specially calibrated chocolate beverage. Their RMR is then monitored at several time points to determine the energy required for digestion. Following this, the study moves into the very-low-calorie diet (VLCD) phase, where participants consume approximately 800 kcal per day using formula meals tailored to meet their nutritional needs despite the calorie restriction. During this 12-week phase, changes in body weight, composition, and metabolic parameters are closely monitored. The final phase of the study is a 12-week weight maintenance period, during which the focus is on sustaining the achieved weight loss. In addition to RMR and dietary assessments, advanced techniques such as metabolomics are employed. Blood, urine, and saliva samples are collected to analyze metabolic profiles and identify potential hormonal biomarkers-such as leptin, FGF21, and adrenaline-that could further differentiate the "thrifty" and "spendthrift" phenotypes. Body composition is also assessed using methods like bioimpedance analysis (BIA), quantitative magnetic resonance imaging (qMR), and air displacement plethysmography (BodPod). By correlating the changes in RMR with metabolic and hormonal markers, the study tests the hypothesis that individuals with a marked RMR decrease during fasting (the "thrifty" phenotype) may experience less weight loss during a hypocaloric diet compared to those with minimal RMR change (the "spendthrift" phenotype). If validated, this approach could allow clinicians to predict weight loss outcomes more accurately and tailor obesity treatments to the individual's unique metabolic profile.

Kiel, Schleswig-Holstein, Germany
RecruitingObservational study

Effect of Sacubitril/Valsartan on Cardiac Function in Hypertensive Patients Stratified by BMI: A Real World Study

The purpose of this study is to investigate the effect of sacubitril/valsartan on cardiac function assessed by cardiac magnetic resonance (CMR) in hypertensive patients stratified by BMI.

Beijing, Beijing Municipality, China